Medtech Company Leverages Bayesian Clinical Trial Design to Address FDA Feedback

Client Challenge

A global medtech company had successfully developed an implant and conducted clinical trials in the European Union, obtaining approval from a Notified Body. The product was classified as a high-risk device because it is an implant. To seek Premarket Approval (PMA) registration in the United States (US), the company initially planned to conduct a US trial, and submitted their design for a single arm non-comparative trial to the Food and Drug Administration (FDA). The company chose a non-comparative trial due to the limited available information on the existing comparators. Following several challenging interactions with the FDA, the agency concluded that the single arm trial could not be accepted as a pivotal trial for the PMA approval.

The company needed help to address the FDA’s feedback; the FDA wanted to see a design that included a comparator and clearly demonstrated the safety and performance of this new device. In addition, the client operated under budget constraints, so the optimal clinical trial design would address both budget considerations and the FDA concerns.

The client partnered with Alira Health to overcome these challenges. Alira Health was chosen for its expertise in highly innovative methods in the development of trial designs combined with experience in regulatory affairs.

Our Approach 

Alira Health’s multidisciplinary team of medical specialists, regulatory experts and statisticians proposed to find the most appropriate comparator from the client’s competitors through a literature review. Conversations with the FDA reviewers were conducted to agree on the comparator to use in this trial based on the result of the research.

Given the lack of patient-level data, all trial designs considered were simulation-guided Bayesian designs to mathematically incorporate historical data drawn from literature. Alira Health’s experts also suggested that this type of design would be more likely to receive a green light from the FDA as it addressed the FDA’s concerns while featuring two to one randomization in a Bayesian framework.

Specifically, the Alira Health team followed these key steps:

• Conducted a meta-analysis of comparators in the literature review
• Reviewed the potential comparators and selected two options
• Considered a wide range of simulation-guided Bayesian clinical trial designs: single arm or randomized, different randomization ratios, superiority trial, and non-inferiority trial, bearing in mind the client’s need to have the smallest possible sample size
• Built six different trial design options and two comparator options for the client to select the one that best fits their budget constraints
• Built and submitted the FDA pre-submission package including a full statistical planning document, analyzed the FDA’s written feedback, and prepared for and managed the meeting with the FDA reviewers

Outcomes 

Alira Health provided the client with a clinical trial design using a Bayesian framework that met their budget constraints and addressed FDA concerns, with confirmation from the FDA that they are willing to greenlight this design. More discussions are ongoing with the FDA as the client expects to receive Investigational Device Exemption approval.

Key Success Factors

Alira Health combined major expertise in cross-functional teams to provide the client with the best possible advice and outcomes. Our Regulatory, Medical Affairs, and Statistics teams worked seamlessly on this project, bringing together specialized expertise in Bayesian trial design with research proficiency and deep knowledge of the FDA’s expectations and goals.

Learn more about Complex Innovative Trial Designs (CIDs).